On June 5, 2013, the U. S. Food and Drug Administration approved lenalidomide capsules (Revlimid?, Celgene Corporation), for the treatment of patients with mantle cell lymphoma (MCL) whose disease has relapsed or progressed after two prior therapies, one of which included bortezomib (Velcade?,Millennium Pharmaceuticals, a wholly-owned subsidiary of Takeda Pharmaceutical Company).
Mantle cell lymphoma (MCL) is a rare subtype of non-Hodgkin?s lymphoma (NHL) occurring in < 10% of patients with NHL.[1, 2, 3,4] MCL is characterized by uncontrolled growth of transformed B lymphocytes that accumulate in the outer edge (i.e., mantle zone) of a lymph node follicle. [2,5] These malignant cells may spread through the blood or lymph system to other sites to develop extranodal disease in the spleen, bone marrow, liver, or gastrointestinal tract.
?There remains a tremendous unmet need for patients with previously-treated mantle cell lymphoma,? said Andre Goy, M.D., M.S., Chairman and Director and Chief of Lymphoma, John Theurer Cancer Center at Hackensack UMC and Chief Science Officer and Director of Research and Innovation at Regional Cancer Care Associates, LLC. ?The approval of lenalidomide delivers a new option, and the first oral therapy in this area of lymphoma.?
The approval was based a single-arm, multicenter clinical trial enrolling 134 patients with mantle cell lymphoma who have relapsed after or were refractory to bortezomib or a bortezomib-containing regimen. All 134 patients received prior treatment with bortezomib and 60% were documented to have disease refractory to bortezomib therapy. Patients received a median of 4 prior therapies for MCL. The median age was 67 years, 81% were male, 96% were white, and 61% had MCL for at least 3 years.
The efficacy endpoints were overall response rate (ORR) and duration of response (DOR). The ORR was defined as the proportion of patients whose best response was complete response (CR), complete response unconfirmed (CRu), or partial response (PR). In the 133 patients who were evaluable for efficacy, the ORR was 26% (95% CI: 18.4, 33.9). CR or CRu was achieved by 9 patients (7%) and 25 patients (19%) achieved a PR. The median DOR for the 34 patients who achieved a CR, CRu, or PR was 16.6 months (95% CI: 7.7, 26.7).
Safety data was evaluated in 134 patients who received at least one dose of lenalidomide. The median duration of therapy was 95 days (range 1-1002) and 78 (58%) of patients received 3 or more cycles of therapy. Seventy-six patients (57%) underwent at least one dose interruption due to adverse events and 51 patients (38%) underwent at least one dose reduction due to adverse events. Twenty-six patients (19%) discontinued treatment due to adverse events.
The most common (greater than or equal to 15%) grade 1-4 adverse reactions included neutropenia, thrombocytopenia, fatigue, anemia, diarrhea, nausea, cough, pyrexia, rash, dyspnea, pruritis, constipation, peripheral edema and leukopenia. The most common (greater than or equal to 5%) grade 3-4 adverse reactions were neutropenia, thrombocytopenia, anemia, pneumonia, leukopenia, fatigue, febrile neutropenia, dyspnea and diarrhea.
Recommended and supplemental application
The recommended dose and schedule for lenalidomide is 25 mg orally once daily on days 1-21 of repeated 28-day cycles. Lenalidomide should be taken at about the same time each day, either with or without food.
The supplemental application also included the approval of a new 20 mg capsule strength.
For more information:
Highlights of Prescribing Information:lenalidomide (Revlimid?)
 A clinical evaluation of the International Lymphoma Study Group classification of non-Hodgkin’s lymphoma. The Non-Hodgkin’s Lymphoma Classification Project. Blood. 1997; 89:3909-3918.
. Goy A, Kahl B. Mantle cell lymphoma: the promise of new treatment options. Crit Rev Oncol Hematol. 2011; 80:69-86.
. Turner JJ, Hughes AM, Kricker A, et al. WHO non-Hodgkin’s lymphoma classification by criterion-based report review followed by targeted pathology review: an effective strategy for epidemiology studies. Cancer Epidemiol Biomarkers Prev. 2005; 14:2213-2219.
. Zhou Y, Wang H, Fang W, et al. Incidence trends of mantle cell lymphoma in the United States between 1992 and 2004. Cancer. 2008; 113:791-798.
. Armitage JO, Weisenburger DD. New approach to classifying non-Hodgkin’s lymphomas: clinical features of the major histologic subtypes. Non-Hodgkin?s Lymphoma Classification Project. Journal of Clinical Oncology. 1998; 8:2780-2795
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